Novel amide-functionalized chloramphenicol base bifunctional organocatalysts for enantioselective alcoholysis of meso-cyclic anhydrides

• Lingjun Xu,
• Shuwen Han,
• Linjie Yan,
• Haifeng Wang,
• Haihui Peng and
• Fener Chen

Beilstein J. Org. Chem. 2018, 14, 309–317, doi:10.3762/bjoc.14.19

• )-GABOB. Keywords: alcoholysis desymmetrization; bifunctional organocatalysis; chloramphenicol base; Introduction Over the past decade, remarkable advances in the utilization of natural products as chiral structural motifs for the design of bifunctional organocatalysts have been achieved. A high

• desired bifunctional Brønsted acid/base reactivity for enantioselective desymmetrization of anhydrides [48][49]. Results and Discussion A series of new chloramphenicol based-amide bifunctional catalysts 7a–q (Scheme 1) were synthesized from the appropriate optically pure (1R,2R)-diamine 6, prepared via

• desymmetrization of meso-cyclic anhydrides. This method proved to be generally applicable on various anhydrides or alcohols to generate the desired monoesters in good yield and enantioselectivity. The application of this method to the synthesis of (S)-GABOB demonstrated the great synthetic potential for

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• enabled the quantitative synthesis of (thio)ureas and guanidines without using bulk solvents and the generation of byproducts, but it has also been established as a means to develop "click-type" chemistry for these classes of compounds and the concept of small molecule desymmetrization. Moreover

• of para-phenylenediamine (p-pda) where steric hindrance is absent, the desymmetrization was more challenging. It was only achieved in 97% 21a in the reaction with less reactive 4-methoxyphenyl isothiocyanate under NaCl dilution and LAG using ethyl acetate. When highly reactive 4-nitrophenyl

• -thiourea 21a with 4-chloro- and 4-nitrophenyl isothiocyanates. This study demonstrated that solid-state ball milling can efficiently be employed for desymmetrization of ortho- and para-phenylenediamines, enabling selective functionalization of small symmetrical molecules through the extension of molecular

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Bifunctional organocatalysts for the asymmetric synthesis of axially chiral benzamides

• Ryota Miyaji,
• Yuuki Wada,
• Akira Matsumoto,
• Keisuke Asano and
• Seijiro Matsubara

Beilstein J. Org. Chem. 2017, 13, 1518–1523, doi:10.3762/bjoc.13.151

• resolution [42][43][44][45][46][47], desymmetrization [48][49][50][51][52][53][54], de novo annulation [55][56][57][58][59][60][61], and point-to-axial chirality transfer [58][59] (for reviews, see references [31][62][63]), motivated us to expand on the utility of this class of small-molecule catalysts. We

Phosphazene-catalyzed desymmetrization of cyclohexadienones by dithiane addition

• Matthew A. Horwitz,
• Elisabetta Massolo and
• Jeffrey S. Johnson

Beilstein J. Org. Chem. 2017, 13, 762–767, doi:10.3762/bjoc.13.75

• Matthew A. Horwitz Elisabetta Massolo Jeffrey S. Johnson Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290, USA 10.3762/bjoc.13.75 Abstract We report a desymmetrization of cyclohexadienones by intramolecular conjugate addition of a tethered dithiane

• ; desymmetrization; dithiane; iminophosphoranes; organocatalysis; phosphazenes; Findings Desymmetrization has become a well-developed strategy for the construction of complex molecular frameworks [1][2][3][4][5][6]. Cyclohexadienones are multipurpose synthetic building blocks that have found a central role in

• desymmetrization methodologies. The functional groups present in these symmetrical molecules allow for a wide array of downstream transformations and they are all formed through a single reaction from cheap and readily available aromatic feedstocks [7][8][9][10][11]. These substrates have been successfully

A new and expeditious synthesis of all enantiomerically pure stereoisomers of rosaprostol, an antiulcer drug

• Wiesława Perlikowska,
• Remigiusz Żurawiński and
• Marian Mikołajczyk

Beilstein J. Org. Chem. 2016, 12, 2234–2239, doi:10.3762/bjoc.12.215

• be prepared from optically inactive meso-tartaric acid through a two-step reaction sequence. It involves a complete desymmetrization during an acid-catalyzed reaction with (+)-camphor and methyl orthoformate and the subsequent treatment of the formed methyl diester with α-phosphonate carbanion

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• diastereocontrol (dr >98:2). Subsequent enzymatic desymmetrization [91] using lipase Amano AK gave the enantiomerically pure acetate 36 in 81% yield (ee >99%). A further three transformations then delivered cis-solamin A (29). Crucial to the success of this approach and its high efficiency is that it takes

• be solved in future investigations. To date there is only a single report on an enantioselective oxidative cyclization of a 1,5-diene using permanganate together with a chiral counter ion. Other strategies use either a chiral auxiliary, a subsequent desymmetrization or start from a chiral 5,6

• cyclization approach to cis-solamin A. Total synthesis of cis-solamin A using a Ru(VIII)-catalyzed oxidative cyclization and enzymatic desymmetrization as the key steps. Donohoe´s double oxidative cyclization approach to cis-sylvaticin. Permanganate-mediated approach to cis-sylvaticin by Brown and co-workers

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• the thiourea group interact with one or two carbonyl groups of phenylbutenoate 2 (Scheme 5). Another catalytic reaction catalyzed by a primary amine-thiourea that leads to multiple chiral centers is the asymmetric desymmetrization of 4,4-disubstituted cyclohexadienones 5, using the Michael addition of

• prochiral ketones 35 or 36, catalyzed by a primary amine-thiourea 37 developed by Jacobsen. The proposed pathway is based on desymmetrization of 35 or 36 by an intramolecular Michael addition of the corresponding enamines to an α,β-unsaturated ester, to yield bicyclic or spiro-bicyclic products 38 and 39

• the stereochemical outcome of the reaction. The same year, two different groups utilized thiourea catalyst 57 to catalyze the desymmetrization of meso anhydrides 58 and 59 through a methanolysis reaction (Scheme 20 and Scheme 21). Chin, Song and co-workers utilized the catalyst in 5–10 mol % catalyst

Recent advances in copper-catalyzed asymmetric coupling reactions

• Fengtao Zhou and
• Qian Cai

Beilstein J. Org. Chem. 2015, 11, 2600–2615, doi:10.3762/bjoc.11.280

• reaction, the trifluoroacetamido moiety present in the ortho position of the aryl halides plays an important role in enantiocontrol (Scheme 15). Copper-catalyzed asymmetric aryl C–N coupling through desymmetrization and kinetic resolution strategies In the past, the asymmetric version of aryl C–N/O/S

• system through an “indirect” way, either by asymmetric desymmetrization or kinetic resolution [40][41][42][43][44]. In most cases, the enantioselectivities were not satisfactory. Recently, a copper catalytic system became another option toward asymmetric N-arylation reactions in term of improving

• enantioselectivity and efficiency. In 2012, Cai et al. [45] developed the first copper-catalyzed asymmetric intramolecular Ullmann C–N coupling reaction through a desymmetrization strategy. The reaction lead to the enantioselective formation of indolines and tetrahydroquinolines in high yields and up to >99% ee

Asymmetric 1,4-bis(ethynyl)bicyclo[2.2.2]octane rotators via monocarbinol functionalization. Ready access to polyrotors

• Cyprien Lemouchi and
• Patrick Batail

Beilstein J. Org. Chem. 2015, 11, 1881–1885, doi:10.3762/bjoc.11.202

• or 8 by Sonogashira coupling reactions (Scheme 4). Route 1 was preferred on account of higher yields. The ester function is necessary to purify the intermediate 13 and isolate 14 with excellent purity. These results demonstrate the viability of our approach of the desymmetrization of 1,4-bis(ethynyl

Stereoselective synthesis of perillaldehyde-based chiral β-amino acid derivatives through conjugate addition of lithium amides

• Zsolt Szakonyi,
• Reijo Sillanpää and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2014, 10, 2738–2742, doi:10.3762/bjoc.10.289

• obtained. These include the selective reduction of β-enamino ester enantiomers [14], enzyme-catalyzed kinetic resolution [15], and a variety of asymmetric syntheses, for example, the enantioselective syntheses of β-lactams followed by ring opening [16][17], or the enantioselective desymmetrization of

A modular phosphate tether-mediated divergent strategy to complex polyols

• Paul R. Hanson,
• Susanthi Jayasinghe,
• Soma Maitra,
• Cornelius N. Ndi and
• Rambabu Chegondi

Beilstein J. Org. Chem. 2014, 10, 2332–2337, doi:10.3762/bjoc.10.242

• ) and cross metathesis (CM) steps of the process as outlined in Scheme 1. This protocol further highlights the utility of phosphate tether mediated desymmetrization of C2-symmetric 1,3-anti-diene-diol subunit to generate polyol scaffolds which would otherwise be difficult to produce via (Z)-and (E

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

Bidirectional cross metathesis and ring-closing metathesis/ring opening of a C₂-symmetric building block: a strategy for the synthesis of decanolide natural products

• Bernd Schmidt and
• Oliver Kunz

Beilstein J. Org. Chem. 2013, 9, 2544–2555, doi:10.3762/bjoc.9.289

• were identified as particularly useful starting materials, because their termini are homotopic. Therefore, desymmetrization can be accomplished by monofunctionalization, making elaborate reagent or catalyst-controlled transformations unnecessary [2]. In this regard, (R,R)-hexa-1,5-diene-3,4-diol (1) [3

• electrocyclic ring opening to carboxylates 6 [25], although a non-concerted pathway can not be excluded (Scheme 1). To the best of our knowledge, metathesis/non-metathesis one flask sequences have not been used before for the two directional elaboration or desymmetrization of C2-symmetric building blocks. In

• would provide a precursor 2 (Scheme 1) for the RCM-ring opening sequence (Scheme 2). Our synthesis of stagonolide E started with a selective protection of one hydroxy group of diol 1 to furnish the known TBS-ether 10 [6][19], because we knew from previous experience that a desymmetrization based solely

Organocatalyzed enantioselective desymmetrization of aziridines and epoxides

• Ping-An Wang

Beilstein J. Org. Chem. 2013, 9, 1677–1695, doi:10.3762/bjoc.9.192

• Ping-An Wang Department of Medicinal Chemistry, School of Pharmacy, Fourth Military Medical University, Changle Xilu 17, Xi-An, 710032, P. R. China 10.3762/bjoc.9.192 Abstract Enantioselective desymmetrization of meso-aziridines and meso-epoxides with various nucleophiles by organocatalysis has

• emerged as a cutting-edge approach in recent years. This review summarizes the origin and recent developments of enantioselective desymmetrization of meso-aziridines and meso-epoxides in the presence of organocatalysts. Keywords: aziridine; desymmetrization; enantioselectivity; epoxide; organocatalysis

• based on transition-metal catalyzed reactions has given rise to a variety of significant achievements both in academic and industrial chemistry [2][3]. Desymmetrization is the modification of a molecule which results in the loss of symmetry elements such as a mirror plane, a center of inversion or a

Study on the total synthesis of velbanamine: Chemoselective dioxygenation of alkenes with PIFA via a stop-and-flow strategy

• Huili Liu,
• Kuan Zheng,
• Xiang Lu,
• Xiaoxia Wang and
• Ran Hong

Beilstein J. Org. Chem. 2013, 9, 983–990, doi:10.3762/bjoc.9.113

• 321004, China 10.3762/bjoc.9.113 Abstract A “stop-and-flow” strategy was developed for the chemoselective dioxygenation of alkenes with a PIFA-initiated cyclization. This method is conceived for the desymmetrization of seco-diene, and a series of substituted 5-hydroxymethyl-γ-lactones were constructed

• after hydrolysis. This strategy also differentiates terminally substituted alkenes and constitutes a potentially novel synthetic approach for the efficient synthesis toward velbanamine. Keywords: alkene; desymmetrization; dioxygenation; lactone; PIFA; velbanamine; Introduction Stictosidine-derived

• terminal alkenes. Although iodolactonization as exemplified in Kita’s elegant synthesis of rubrenolide resulted in a practical approach on desymmetrization [45], the subsequent hydrolysis still required an extra step to reveal the proper hydroxy group. Results and Discussion The pathway of cyclization

NHC-catalysed highly selective aerobic oxidation of nonactivated aldehydes

• Lennart Möhlmann,
• Stefan Ludwig and
• Siegfried Blechert

Beilstein J. Org. Chem. 2013, 9, 602–607, doi:10.3762/bjoc.9.65

• mild method for more interesting chemoselective transformations. Therefore, several substrates were oxidised under our conditions bearing either a second alcohol or aldehyde functionality. Desymmetrization of dialdehydes by selective oxidation is an important challenge, since symmetric dialdehydes are

Design and synthesis of quasi-diastereomeric molecules with unchanging central, regenerating axial and switchable helical chirality via cleavage and formation of Ni(II)–O and Ni(II)–N coordination bonds

• Vadim A. Soloshonok,
• José Luis Aceña,
• Hisanori Ueki and
• Jianlin Han

Beilstein J. Org. Chem. 2012, 8, 1920–1928, doi:10.3762/bjoc.8.223

• environment upon its configurational stabilization in complexes 5 and 6. Results and Discussion To build the real molecules to this design, we explored the preparation of imino–carbonyl ligands 13 (Scheme 3) by desymmetrization of achiral carbonyl–carbonyl ligands 12. Compounds 12 were prepared in the

• central, axial and helical chirality. Preparation of imino–carbonyl ligands 13 by desymmetrization of achiral carbonyl–carbonyl ligands 12. Preparation of complexes 14a,b and 15 by reactions of ligands 12 with glycine. Oxidation of enolates 16 and formation of complexes 19 and 20. Supporting Information

Asymmetric desymmetrization of meso-diols by C₂-symmetric chiral 4-pyrrolidinopyridines

• Hartmut Schedel,
• Keizo Kan,
• Yoshihiro Ueda,
• Kenji Mishiro,
• Keisuke Yoshida,
• Takumi Furuta and
• Takeo Kawabata

Beilstein J. Org. Chem. 2012, 8, 1778–1787, doi:10.3762/bjoc.8.203

• pyrrolidinopyridine framework as a catalytic site. Some of these organocatalysts effectively promoted asymmetric desymmetrization of meso-diols via enantioselective acylation. Keywords: acylation; desymmetrization; hydrogen bond; meso-diol; nucleophilic catalyst; organocatalysis; Introduction Since the pioneering

• pyrrolidine ring such as 3 were prepared from trans-4-hydroxy-L-proline. These catalysts were found to be moderately effective for the asymmetric desymmetrization of meso-diols [11]. C2-Symmetric PPY-catalyst 4 was found to be effective for the chemo- and regioselective acylation of carbohydrates [12][14][16

• ] and the chemoselective monoacylation of linear diols [17]. Here, we report the asymmetric desymmtrization of meso-diols by C2-symmetric PPY catalysts [20]. The effects of the functional side chains at C(2) and C(5) on the efficiency of the asymmetric desymmetrization are discussed. Some of the results

The crystal structure of the Dess–Martin periodinane

• Albert Schröckeneder,
• Desiree Stichnoth,
• Peter Mayer and
• Dirk Trauner

Beilstein J. Org. Chem. 2012, 8, 1523–1527, doi:10.3762/bjoc.8.172

• significantly different bond lengths (I1–O5 = 2.0670(13) Å, I1–O7 = 2.1141(13) Å), which desymmetrizes the molecule overall. This desymmetrization cannot be attributed to crystal-packing effects since it is also apparent in a structural model of 1 calculated by using DFT theory at the PBE0/LANL2DZdp level [10

Organocatalytic asymmetric addition of malonates to unsaturated 1,4-diketones

• Sergei Žari,
• Tiiu Kailas,
• Marina Kudrjashova,
• Mario Öeren,
• Ivar Järving,
• Toomas Tamm,
• Margus Lopp and
• Tõnis Kanger

Beilstein J. Org. Chem. 2012, 8, 1452–1457, doi:10.3762/bjoc.8.165

• ]. Therefore, new asymmetric additions of C-nucleophiles to unsaturated 1,4-diketones are highly in demand. The asymmetric desymmetrization of symmetric unsaturated 1,4-diketones is a very challenging target. si-Attack on one carbon atom of the double bond and re-attack on the other leads to the same

• investigated the organocatalytic approach to the asymmetric desymmetrization of the title compounds with malonates. Three types of organocatalysts providing noncovalent interactions were used for this purpose: Cinchona alkaloids (I–V), thiourea derivatives (VI, VII) and squaramide derivatives (VIII, IX

• -enantiomer. Conclusion We have developed a highly enantioselective method for the desymmetrization of aromatic unsaturated 1,4-diketones through organocatalytic reactions with malonates. The reaction is catalyzed by thiourea and squaramide derivatives with Cinchona alkaloids and affords products in very high

Synthesis of chiral sulfoximine-based thioureas and their application in asymmetric organocatalysis

• Marcus Frings,
• Isabelle Thomé and
• Carsten Bolm

Beilstein J. Org. Chem. 2012, 8, 1443–1451, doi:10.3762/bjoc.8.164

• backbone the sulfonimidoyl moiety leads to organocatalysts showing good reactivity in the catalytic desymmetrization of a cyclic meso-anhydride and moderate enantioselectivity in the catalytic asymmetric Biginelli reaction. Straightforward synthetic routes provide the newly designed thiourea-sulfoximine

• representative of each class was briefly tested in the desymmetrization of anhydride 4. Under the conditions described above for organocatalyst (S)-3 two catalyses were performed with (S)-12 (10 mol %) and (RS,SC)-19 (5 mol %). Whereas benzene-bridged sulfonimidoyl-containing thiourea (S)-12 provided the product

• hemiesters (5/ent-5). Apparently, both thioureas proved inappropriate for this reaction, and no further efforts were made to improve the anhydride desymmetrization with these types of organocatalysts. Next, the catalysis screening was focused on Biginelli reactions, which provide access to dihydropyrimidines

Bromine–lithium exchange: An efficient tool in the modular construction of biaryl ligands

• Laurence Bonnafoux,
• Frédéric R. Leroux and
• Françoise Colobert

Beilstein J. Org. Chem. 2011, 7, 1278–1287, doi:10.3762/bjoc.7.148

• routes to synthetically challenging aryl halide precursors have been devised. A. Alexakis et al. recently achieved a significant breakthrough. They succeeded in the desymmetrization of prochiral polybrominated [32][51] compounds by an asymmetric bromine–lithium exchange in the presence of a

• stoichiometric amount of chiral diamines. An enantiomeric excess of up to 63% was obtained [67]. H. Kagan et al. reported the desymmetrization of prochiral aromatic or vinylic dihalide substrates by halogen–metal exchange in the presence of a stoichiometric amount of diamines, with enantiomeric excess up to 26

Brønsted acid-promoted azide–olefin [3 + 2] cycloadditions for the preparation of contiguous aminopolyols: The importance of disiloxane ring size to a diastereoselective, bidirectional approach to zwittermicin A

• Hubert Muchalski,
• Ki Bum Hong and
• Jeffrey N. Johnston

Beilstein J. Org. Chem. 2010, 6, 1206–1210, doi:10.3762/bjoc.6.138

• pure (−)-zwittermicin A (1) is based on a short synthesis of the C9–C15 aminopolyol core that takes advantage of its underlying C2 symmetry, as outlined in Scheme 1. Desymmetrization and functionalization of the bis(oxazolidine dione) 2 provides us with a foundation for the synthesis of 1 and would

Enantioselective synthesis of tricyclic amino acid derivatives based on a rigid 4-azatricyclo[5.2.1.0^2,6]decane skeleton

• Matthias Breuning,
• Tobias Häuser,
• Christian Mehler,
• Christian Däschlein,
• Carsten Strohmann,
• Andreas Oechsner and
• Holger Braunschweig

Beilstein J. Org. Chem. 2009, 5, No. 81, doi:10.3762/bjoc.5.81

• and 8 were successfully accomplished in 9–10 steps starting with inexpensive endo-carbic anhydride (10). The key stereochemical step was the desymmetrization of the meso-alkene 11 using Hayashi’s hydrosilylation/oxidation procedure, which provided the endo-alcohol 12 in 85% ee. The target molecules